Our principal objective is to determine the interrelationship of C-type viruses to autoimmune disease and neoplasia. New Zealand Black (NZB) mice offer an excellent animal model system for this study; they have a disease syndrome similar to lupus erythematosus in man and develop reticulum cell sarcomas late in life. We have isolated a C-type virus from NZB mice which, because it can be propagated only in cells foreign to the host species, has been called a xenotropic (X-tropic) virus. Since similar viruses have been recovered from other mice, it is probably a universal endogenous virus of mice. Our aim is to understand the role of these endogenous viruses in normal life processes including embryogenesis, differentiation, cell aging, and cancer. We shall be studying the mechanism by which the presence of this virus is regulated in NZB and other mouse cells, and whether its increased expression in NZB mice is related to their autoimmune disease and neoplasia. We shall also continue our investigation of the host response to this virus which has been recognized as mediated by anti-viral factors in most mouse sera. BIBLIOGRAPHIC REFERENCE: Levy, J.A. Host range of murine xenotropic virus: Replication in avian cells. Nature 253: 140:142, 1975. Levy, J.A., Hartley, J.W., Rowe, W.P. and Huebner, R.J. Studies of FBJ osteosarcoma virus in tissue culture. II. Auto-inhibition of focus formation. J. Natl. Cancer Inst. 54: 615-619, 1975.